Project Title: A microreactor chip platform for quantitative analysis of unsaturated aldehydes in exhaled breath 7. Project Summary/Abstract Lung cancer has the highest mortality of all types of cancer. Early lung cancer detection is a key factor for increasing survival rates of lung cancer patients. The analysis of exhaled breath samples has great potential to become a powerful non-invasive screening and diagnostic tool for early lung cancer detection. A number of recent publications have indicated that certain volatile organic compounds (VOCs) in exhaled breath may be lung cancer metabolic output. However, there are some critical challenges for the analysis of breath VOCs that hinder the use of breath analysis technology for clinical applications. These challenges include trace levels of VOCs in breath much lower than the detection limits of most current analytical instruments; the complexity of sorting a large number of VOCs; and matrix interferences imparted by abundant and/or structurally similar VOCs unrelated to cancers. These challenges make it very difficult to identify true metabolic markers of lung cancers. We have developed a microreactor approach that uses a quaternary aminooxy coating for chemoselective capture of carbonyl compounds in exhaled breath. Four carbonyl compounds have been identified to have significantly higher concentrations in the breath of lung cancer patients than in the breath of healthy control subjects. However, the slow reaction kinetics of the quaternary aminooxy coating with unsaturated aldehydes and unstable nature of these compounds make the microreactor technology inadequate for quantification of key unsaturated aldehydes in exhaled breath. Many unsaturated aldehydes in exhaled breath are related to lung cancer dysfunction-induced oxidative stress. Unfortunately, there is no current technology that can be used to adequately measure unsaturated aldehydes in exhaled breath. The goal of this project is to develop a microreactor chip platform technology for quantitative analysis of unsaturated aldehydes in exhaled breath for differentiation of early lung cancer from benign pulmonary nodules. The technology will overcome all critical challenges of current breath analysis technologies and enable quantitative analysis of unsaturated aldehydes. The goal will be fulfilled by the following two specific aims: Specific Aim 1. Develop a novel microreactor platform for accurate measurement of unsaturated aldehydes in exhaled breath; Specific Aim 2. Establish novel algorithms for diagnosis of lung cancer by breath analysis. The proposed microreactor chip platform for quantitative analysis of unsaturated aldehydes will be transformative because it will enable measurement and identification of lung cancer metabolic aldehydes and establish a non-invasive tool for differentiation of lung cancer from benign pulmonary nodules. The microreactor chip enabled quantitative analysis of unsaturated aldehydes in breath can also be used with low dose CT screening for detection of early lung cancer and differentiation of lung cancer from benign pulmonary nodules. The proposed technology will be superior to current breath analysis approaches because of four critical innovations: (1) diagnosis of lung cancer by quantitative measurement of cancer metabolic unsaturated aldehydes in exhaled breath; (2) a novel microreactor for decreasing sample evacuation time; (3) optimized chemoselective coatings for efficient capture of unsaturated aldehydes; and (4) separation of analyte adducts and quantitation by UHPLC-MS.